Syntaxin 11 is required for NK and CD8+ T-cell cytotoxicity and neutrophil degranulation

Orietta D'Orlando, Fang Zhao, Brigitte Kasper, Zane Orinska, Jürgen Müller, Irm Hermans-Borgmeyer, Gillian M. Griffiths, Udo Zur Stadt, Silvia Bulfone-Paus

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Syntaxin 11 (STX11) controls vesicular trafficking and is a key player in exocytosis. Since Stx11 mutations are causally associated with a familial hemophagocytic lymphohistio-cytosis, we wanted to clarify whether STX11 is functionally important for key immune cell populations. This was studied in primary cells obtained from newly generated Stx11-/- mice. Our data revealed that STX11 is not only widely expressed in different immune cells, but also induced upon LPS or IFN-γ treatment. However, Stx11 deficiency does not affect macrophage phagocytic function and cytokine secretion, mast cell activation, or antigen presentation by DCs. Instead, STX11 selectively controls lymphocyte cytotoxicity in NK and activated CD8+ T cells and degranulation in neutrophils. Stx11-/- NK cells and CTLs show impaired degranulation, despite a comparable activation, maturation and expression of the complex-forming partners MUNC18-2 and VTI1B. In addition, Stx11-/- CTLs and NK cells produce abnormal levels of IFN-γ. Since functional reconstitution rescues the defective phenotype of Stx11-/- CTLs, we suggest a direct, specific and key role of STX11 in controlling lymphocyte cytotoxicity, cytokine production and secretion. Finally, we show that these mice are a very useful tool for dissecting the role of STX11 in vesicular trafficking and secretion.

Original languageEnglish
Pages (from-to)194-208
Number of pages15
JournalEuropean Journal of Immunology
Volume43
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • CTL
  • Cytokines
  • Exocytosis
  • N-ethylmaleimide-sensitive factor attachment protein receptor

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